title: Mapping water exchange rates in rat tumor xenografts using the late-stage uptake following bolus injections of contrast agent.
abstract: OBJECTIVE
  To map the intra-to-extracellular water exchange rate constant in rat xenografts using a two-compartment model of relaxation with water exchange and a range of contrast agent concentrations and compare with histology.
  
  
  METHODS
  MDA-MB-231 cells were xenografted into six nude rats. Three bolus injections of gadodiamide were administered. When uptake in the tumor demonstrated a steady-state, T1 data were acquired by spoiled gradient recalled acquisitions at four flip angles. A global fit of data to a two-compartment model incorporating exchange was performed, assuming a distribution volume of 20% of the rat.
  
  
  RESULTS
  Voxels that did not reach steady-state and were excluded from parametric maps tended to be in large necrotic areas. TUNEL-negative (nonapoptotic) regions tended to have well-defined error bounds, with an average intra-to-extracellular exchange rate constant of 0.6 s(-1) . Apoptotic regions had higher exchange, but poorly determined upper bounds, with goodness of fit similar to that for a model assuming infinitely fast exchange. A lower bound of >3 s(-1) was used to establish voxels where the exchange rate constant was fast despite a large upper bound.
  
  
  CONCLUSIONS
  Water exchange rates were higher in apoptotic regions, but examination of statistical errors was an important step in the mapping process.
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Bailey
authors.forename: Firas
authors.initials: F
authors.lastname: Moosvi
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stanisz
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011923:Rats, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA
keywords: DCE-MRI; quantitative MRI; tumor response; two-compartment model; water exchange rate